Hematologics, Inc., Seattle, Washington, USA.
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Cytometry B Clin Cytom. 2023 Jul;104(4):311-318. doi: 10.1002/cyto.b.22118. Epub 2023 Apr 4.
Detection of measurable residual disease detection (MRD) by flow cytometry after the first course of chemotherapy is a standard measure of early response in patients with acute myeloid leukemia (AML). Myeloid leukemia associated with Down Syndrome (ML-DS) is a distinct form of AML. Differences in steady-state and regenerating hematopoiesis between patients with or without DS are not well understood. This understanding is essential to accurately determine the presence of residual leukemia in patients with ML-DS.
A standardized antibody panel defined quantitative antigen expression in 115 follow-up bone marrow (BM) aspirates from 45 patients following chemotherapy for ML-DS or DS precursor B-cell acute lymphoblastic leukemia (B-ALL-DS) with the "difference from normal (ΔN)" technique. When possible, FISH and SNP/CGH microarray studies were performed on sorted cell fractions.
93% of BM specimens submitted post chemotherapy had a clearly identifiable CD34 CD56 population present between 0.06% and 2.6% of total non-erythroid cells. An overlapping CD34 HLA-DR population was observed among 92% of patients at a lower frequency (0.04%-0.8% of total non-erythroid cells). In B-ALL-DS patients, the same CD34 CD56 HLA-DR expression was observed. FACS-FISH/Array studies demonstrated no residual genetic clones in the DS-specific myeloid progenitor cells.
Non-malignant myeloid progenitors in the regenerating BM of patients who have undergone chemotherapy for either ML-DS or B-ALL-DS express an immunophenotype that is different from normal BM of non-DS patients. Awareness of this DS-specific non-malignant myeloid progenitor is essential to the interpretation of MRD by flow cytometry in patients with ML-DS.
急性髓细胞白血病（AML）患者在第一疗程化疗后通过流式细胞术检测可测量残留疾病（MRD）是早期反应的标准测量方法。伴有唐氏综合征（DS）的髓系白血病（ML-DS）是一种独特的 AML 形式。患有或不患有 DS 的患者稳态和再生造血之间的差异尚未得到很好的理解。这种理解对于准确确定 ML-DS 患者残留白血病的存在至关重要。
采用标准化抗体面板，使用“与正常的差异（ΔN）”技术，对 45 例 ML-DS 或 DS 前体 B 细胞急性淋巴细胞白血病（B-ALL-DS）患者化疗后 115 次随访骨髓（BM）抽吸物中的定量抗原表达进行定义。在可能的情况下，对分选细胞进行 FISH 和 SNP/CGH 微阵列研究。
93%的化疗后 BM 标本中存在明显可识别的 CD34 CD56 群体，其存在于总非红细胞细胞的 0.06%至 2.6%之间。92%的患者观察到重叠的 CD34 HLA-DR 群体，频率较低（总非红细胞细胞的 0.04%-0.8%）。在 B-ALL-DS 患者中，观察到相同的 CD34 CD56 HLA-DR 表达。FACS-FISH/Array 研究表明，DS 特异性髓系祖细胞中不存在残留的遗传克隆。
接受 ML-DS 或 B-ALL-DS 化疗的患者再生 BM 中的非恶性髓系前体细胞表达的免疫表型与非 DS 患者的正常 BM 不同。了解这种 DS 特异性非恶性髓系前体是解释 ML-DS 患者流式细胞术 MRD 的关键。
